Characterizing the symptomatology and pathophysiology of allergic rhinitis using a nasal allergen challenge model - a subset of the allergic rhinitis microbiome study.

Background: Since 2015, our nasal allergen challenge (NAC) protocol has been used to investigate the pathophysiology of allergic rhinitis (AR) with various allergens. However, we have yet to publish a comprehensive examination of the pathophysiology associated with AR to ragweed pollen.

Methods: Nineteen ragweed pollen allergic and 12 healthy (nonallergic) control participants from Kingston, Ontario, Canada, completed the NAC to ragweed pollen extract out-of-season. Total nasal symptom score (TNSS) and percent fall in peak nasal inspiratory flow (PNIF) were collected up to 48 h post-exposure. Nasal fluid and serum samples were collected post-exposure, and white blood cell differential counts, serum ragweed-specific and total immunoglobulin-E (IgE), and nasal cytokine concentrations were analyzed. Statistical tests were performed using GraphPad Prism 10.4.0.

Results: The mean TNSS and percent PNIF fall from baseline were significantly higher in participants with ragweed pollen allergy compared to nonallergic controls up to 24 h (P ≤ 0.05) and 12 h (P ≤ 0.05) post-NAC, respectively. Nasal eosinophils significantly increased in allergic participants at 6 h (P = 0.0010) and 24 h (P = 0.0049), while peripheral blood eosinophil percentages decreased significantly at 6 h compared to baseline (P = 0.0499). The specific to total IgE ratio for allergic participants significantly increased 1 h and 24 h (P = 0.0022 and P = 0.0034, respectively) post-NAC, with a decrease at 6 h compared to both 1 h and 24 h (P = 0.0224 and P = 0.0316, respectively). Allergic and nonallergic participants had significantly different cytokine profiles, particularly IL-4, IL-5, IL-6, IL-13, MIP-1β, and TNF-α.

Conclusions: This study confirms the effectiveness of our NAC protocol in eliciting clinical and biological responses in ragweed-allergic participants, particularly highlighting eosinophil activity, IgE, and cytokine dynamics. Future research should investigate the roles of specific IgE, IL-4, and eosinophil activation in allergic inflammation. Additionally, this NAC study population provides a strong foundation for examining the nasal microbiome in AR. Longitudinal studies exploring the relationship between allergic responses and microbiome shifts could offer deeper insights into the underlying mechanisms of disease.